tbuckley/cabot-search huggingface dataset:
LTBK-02. Safety of growth hormone replacement therapy in childhood craniopharyngioma
Authors: Jiska van Schaik, Eline Kormelink, Netteke Schouten-van Meeteren, Evelien de Vos-Kerkhof, Boudewijn Bakker, Marta Fiocco, Eelco Hoving, Wim Tissing, Hanneke van Santen
Journal: Neuro-Oncology (2022)

Abstract Introduction: Treatment for childhood-onset craniopharyngioma (cCP) has shifted from complete to limited resection aiming to avoid additional hypothalamic morbidity. Up to 90% of cCP patients develop growth hormone deficiency (GHD). GH replacement therapy (GHRT) is of high importance for linear growth and metabolic state. Hardly any studies evaluated the optimal time to start GHRT in relation to tumor progression or recurrence. Our aim was to assess the effect of GHRT in cCP on tumor progression/recurrence. Methods: Patients with cCP diagnosed between 2001 and 2022, with at least one year of follow-up were included. Tumor progression/recurrence was defined as tumor progression/recurrence requiring intervention. Kaplan Meier and multivariable cox regression analyses were estimated for tumor progression/recurrence. Comparison was made between cCP patients with GHRT and without GHRT. Of the cCP patients receiving GHRT, those given GHRT ≤ 1 year of cCP diagnosis were compared to those given GHRT &amp;gt;1 year after cCP diagnosis. Results: Of 59 cCP patients, 52 were diagnosed with GHD and 51 (86.4%) received GHRT. Sixteen cCP patients (31.4%) developed tumor progression/recurrence during GHRT compared to four cCP patients (50.0%) without GHRT. Mean progression free survival (PFS) did not differ between cCP patients with or without GHRT (GHRT: 5.55 years 95% CI 3.74 - 7.36 vs. no GHRT: 3.69 years 95% CI 1.44 - 5.93). Of cCP patients who started GHRT ≤1 year after cCP diagnosis, 36.4% developed tumor progression/recurrence compared to 27.6% of cCP patients who received GHRT &amp;gt; 1 year after diagnosis (PFS: 8.45 years CI 95% 5.54 – 11.36 vs. 7.99 years CI 95% 6.03 – 9.94). Limited surgery was associated to tumor progression/recurrence (HR 6.99 CI 95% 2.10 – 23.25). Conclusion: GHRT does not seem to influence tumor progression/recurrence in cCP. These results support early initiation of GHRT in cCP patients to optimize linear growth and metabolic outcome.
Premenopausal Vaginitis
Authors: Kristin Walter
Journal: JAMA (2022)

Premenopausal VaginitisVaginitis is inflammation or infection of the vagina.Common symptoms of vaginitis include itching, irritation, and abnormal vaginal discharge that may have an unpleasant smell.Some patients may experience vaginal pain with sexual intercourse.The 3 most common causes of premenopausal vaginitis are vulvovaginal candidiasis, bacterial vaginosis, and trichomoniasis, which account for more than 70% of cases of vaginitis. How Is Vaginitis Diagnosed?Vaginitis is typically diagnosed through a patient's history, physical examination, pH testing of vaginal discharge, and examination of vaginal discharge under a microscope (microscopy).In addition, vaginal or cervical swabs obtained by a clinician or patient can be analyzed using advancedlaboratorytechniques(nucleicacidamplificationtesting[NAAT]) to identify organisms that cause vaginitis and to test for gonorrhea and chlamydia,whicharecommoncausesofsexuallytransmittedinfections.
New Data on Opioid Dose Reduction—Implications for Patient Safety
Authors: Stefan G. Kertesz, Allyson L. Varley
Journal: JAMA Network Open (2022)

Joshua J. Fenton, MD, MPH; Elizabeth Magnan, MD, PhD; Iraklis Erik Tseregounis, PhD; Guibo Xing, PhD; Alicia L. Agnoli, MD, MPH, MHS; Daniel J. Tancredi, PhD
Association Between Insulin Resistance and Cardiovascular Disease Risk Varies According to Glucose Tolerance Status: A Nationwide Prospective Cohort Study
Authors: Tiange Wang, Mian Li, Tianshu Zeng, Ruying Hu, Yu Xu, Min Xu, Zhiyun Zhao, Yuhong Chen, Shuangyuan Wang, Hong Lin, Xuefeng Yu, Gang Chen, Qing Su, Yiming Mu, Lulu Chen, Xulei Tang, Li Yan, Guijun Qin, Qin Wan, Zhengnan Gao, Guixia Wang, Feixia Shen, Zuojie Luo, Yingfen Qin, Li Chen, Yanan Huo, Qiang Li, Zhen Ye, Yinfei Zhang, Chao Liu, Youmin Wang, Shengli Wu, Tao Yang, Huacong Deng, Jiajun Zhao, Lixin Shi, Guang Ning, Yufang Bi, Weiqing Wang, Jieli Lu
Journal: Diabetes Care (2022)

OBJECTIVE To investigate whether the association between insulin resistance and cardiovascular disease (CVD) differs by glucose tolerance status. RESEARCH DESIGN AND METHODS We analyzed a nationwide sample of 111,576 adults without CVD at baseline, using data from the China Cardiometabolic Disease and Cancer Cohort Study. Insulin resistance was estimated by sex-specific HOMA of insulin resistance (HOMA-IR) quartiles for participants with normal glucose tolerance, prediabetes, or diabetes, separately, and by 1 SD of HOMA-IR for the overall study participants. We used Cox proportional hazards models to examine the association between insulin resistance and incident CVD according to glucose tolerance status and evaluate the CVD risk associated with the combined categories of insulin resistance and obesity in prediabetes and diabetes, as compared with normal glucose tolerance. Models were adjusted for age, sex, education attainment, alcohol drinking, smoking, physical activity, and diet quality. RESULTS In participants with normal glucose tolerance, prediabetes, and diabetes defined by three glucose parameters, multivariable-adjusted hazard ratios (95% CIs) for incident CVD associated with the highest versus the lowest quartile of HOMA-IR were 1.03 (0.82–1.30), 1.23 (1.07–1.42), and 1.61 (1.30–2.00), respectively; the corresponding values for CVD per 1-SD increase in HOMA-IR were 1.04 (0.92–1.18), 1.12 (1.06–1.18), and 1.15 (1.09–1.21), respectively (P for interaction = 0.011). Compared with participants with normal glucose tolerance, in participants with prediabetes, the combination of the highest HOMA-IR quartile and obesity showed 17% (95% CI 2–34%) higher risk of CVD, while the combination of the lowest two HOMA-IR quartiles and nonobesity showed 15–17% lower risk of CVD. In participants with diabetes, the upper two HOMA-IR quartiles exhibited 44–77% higher risk of CVD, regardless of obesity status. Consistent findings were observed for glucose tolerance status defined by different combinations of glycemic parameters. CONCLUSIONS Glucose intolerance status exacerbated the association between insulin resistance and CVD risk. Compared with adults with normal glucose tolerance, adults with prediabetes who were both insulin resistant and obese exhibited higher risks of CVD, while in adults with diabetes, the CVD risk related to insulin resistance remained, regardless of obesity.
U.S. Trends in Registration for Medical Cannabis and Reasons for Use From 2016 to 2020
Authors: Kevin F. Boehnke, Owen Dean, Rebecca L. Haffajee, Avinash Hosanagar
Journal: Annals of Internal Medicine (2022)

Background: Cannabis policy liberalization has increased cannabis availability for medical or recreational purposes. Up-to-date trends in medical cannabis licensure can inform clinical policy and care. Objective: To describe recent trends in medical cannabis licensure in the United States. Design: Ecological study with repeated measures. Setting: State registry data via state reports and data requests on medical cannabis licensure from 2016 to 2020. Participants: Medical cannabis patients (persons with medical cannabis licenses) in the United States. Measurements: Total patient volume, patients per 10 000 of total population, and patient-reported qualifying conditions (that is, symptoms or conditions qualifying patients for licensure)—including whether these symptoms align with current therapeutic evidence of cannabis–cannabinoid efficacy. Results: In 2020, 26 states and Washington, DC reported patient numbers, and 19 states reported patient-reported qualifying conditions. Total enrolled patients increased approximately 4.5-fold from 678 408 in 2016 to 2 974 433 in 2020. Patients per 10 000 total population generally increased from 2016 to 2020, most dramatically in Oklahoma (927.1 patients per 10 000 population). However, enrollment increased in states without recreational legalization (that is, medical-only states), whereas enrollment decreased in 5 of 7 with recreational legalization (that is, recreational states). In 2020, 68.2% of patient-reported qualifying conditions had substantial or conclusive evidence of therapeutic value versus 84.6% in 2016. Chronic pain was the most common patient-reported qualifying condition in 2020 (60.6%), followed by posttraumatic stress disorder (10.6%). Limitation: Missing state data; lack of rationale for discontinuing medical cannabis licensure. Conclusion: Enrollment in medical cannabis programs approximately increased 4.5-fold from 2016 to 2020, although enrollment decreased in recreational states. Use for conditions or symptoms without a strong evidence basis increased from 15.4% (2016) to 31.8% (2020). Thoughtful regulatory and clinical strategies are needed to effectively manage this rapidly changing landscape. Primary Funding Source: National Institute on Drug Abuse of the National Institutes of Health.
Improving Physical Activity in Pediatric Cancer Survivors—Engaging Parents
Authors: Katie A. Devine, Gary Kwok
Journal: JAMA Network Open (2022)

Ankie Tan Cheung, PhD, MPhil, BN, RN; William Ho Cheung Li, PhD, MPhil, BN, RN; Laurie Long Kwan Ho, PhD, MPhil, BN, RN; Godfrey Chi-Fung Chan, DMD, MD; Huen Sum Lam, PhD, MPhil, MScSoc, BA, DipEd; Joyce Oi Kwan Chung, PhD, BN, RN
Subcutaneous delivery of a dendrimer-BH3 mimetic improves lymphatic uptake and survival in lymphoma
Authors: Orlagh M. Feeney, Katie Ardipradja, Ka Fung Noi, Dharmini Mehta, Robert De Rose, Daniel Yuen, Angus P.R. Johnston, Lee Kingston, Cecilia Ericsson, Charles S. Elmore, Richard Hufton, David J. Owen, Marianne B. Ashford, Christopher J.H. Porter
Journal: Journal of Controlled Release (2022)
Analysis of Thromboembolic and Thrombocytopenic Events After the AZD1222, BNT162b2, and MRNA-1273 COVID-19 Vaccines in 3 Nordic Countries
Authors: Jacob Dag Berild, Vilde Bergstad Larsen, Emilia Myrup Thiesson, Toni Lehtonen, Mari Grøsland, Jon Helgeland, Jan Wolhlfahrt, Jørgen Vinsløv Hansen, Arto A. Palmu, Anders Hviid
Journal: JAMA Network Open (2022)

Vaccinations are paramount to halt the COVID-19 pandemic, and safety data are essential to determine the risk-benefit ratio of each COVID-19 vaccine.To evaluate the association between the AZD1222, BNT162b2, and mRNA-1273 vaccines and subsequent thromboembolic and thrombocytopenic events.This self-controlled case series used individual-level data from national registries in Norway, Finland, and Denmark. Participants included individuals with hospital contacts because of coronary artery disease, coagulation disorders, or cerebrovascular disease between January 1, 2020, and May 16, 2021.AZD1222, BNT162b2, or mRNA-1273 vaccine.Relative rate (RR) of hospital contacts for coronary artery disease, coagulation disorders, or cerebrovascular disease in a 28-day period following vaccination compared with the control period prior to vaccination.We found 265 339 hospital contacts, of whom 112 984 [43%] were for female patients, 246 092 [93%] were for patients born in 1971 or earlier, 116 931 [44%] were for coronary artery disease, 55 445 [21%] were for coagulation disorders, and 92 963 [35%] were for cerebrovascular disease. In the 28-day period following vaccination, there was an increased rate of coronary artery disease following mRNA-1273 vaccination (RR, 1.13 [95% CI, 1.02-1.25]), but not following AZD1222 vaccination (RR, 0.92 [95% CI, 0.82-1.03]) or BNT162b2 vaccination (RR, 0.96 [95% CI, 0.92-0.99]). There was an observed increased rate of coagulation disorders following all 3 vaccines (AZD1222: RR, 2.01 [95% CI, 1.75-2.31]; BNT162b2: RR, 1.12 [95% CI, 1.07-1.19]; and mRNA-1273: RR, 1.26 [95% CI, 1.07-1.47]). There was also an observed increased rate of cerebrovascular disease following all 3 vaccines (AZD1222: RR, 1.32 [95% CI, 1.16-1.52]; BNT162b2: RR, 1.09 [95% CI, 1.05-1.13]; and mRNA-1273: RR, 1.21 [95% CI, 1.09-1.35]). For individual diseases within the main outcomes, 2 notably high rates were observed: 12.04 (95% CI, 5.37-26.99) for cerebral venous thrombosis and 4.29 (95% CI, 2.96-6.20) for thrombocytopenia, corresponding to 1.6 (95% CI, 0.6-2.6) and 4.9 (95% CI, 2.9-6.9) excess events per 100 000 doses, respectively, following AZD1222 vaccination.In this self-controlled case series, there was an increased rate of hospital contacts because of coagulation disorders and cerebrovascular disease, especially for thrombocytopenia and cerebral venous thrombosis, following vaccination with AZD1222. Although increased rates of several thromboembolic and thrombocytopenic outcomes following BNT162b2 and mRNA-1273 vaccination were observed, these increases were less than the rates observed after AZD1222, and sensitivity analyses were not consistent. Confirmatory analysis on the 2 mRNA vaccines by other methods are warranted.
Loss of hepatic DRP1 exacerbates alcoholic hepatitis by inducing megamitochondria and mitochondrial maladaptation
Authors: Xiaowen Ma, Allen Chen, Luma Melo, Ana Clemente‐Sanchez, Xiaojuan Chao, Ali Reza Ahmadi, Brandon Peiffer, Zhaoli Sun, Hiromi Sesaki, Tiangang Li, Xiaokun Wang, Wanqing Liu, Ramon Bataller, Hong‐Min Ni, Wen‐Xing Ding
Journal: Hepatology (2022)

Background and Aims: Increased megamitochondria formation and impaired mitophagy in hepatocytes have been linked to the pathogenesis of alcohol‐associated liver disease (ALD). This study aims to determine the mechanisms by which alcohol consumption increases megamitochondria formation in the pathogenesis of ALD. Approach and Results: Human alcoholic hepatitis (AH) liver samples were used for electron microscopy, histology, and biochemical analysis. Liver‐specific dynamin‐related protein 1 (DRP1; gene name DNM1L, an essential gene regulating mitochondria fission ) knockout (L‐DRP1 KO) mice and wild‐type mice were subjected to chronic plus binge alcohol feeding. Both human AH and alcohol‐fed mice had decreased hepatic DRP1 with increased accumulation of hepatic megamitochondria. Mechanistic studies revealed that alcohol feeding decreased DRP1 by impairing transcription factor EB–mediated induction of DNM1L . L‐DRP1 KO mice had increased megamitochondria and decreased mitophagy with increased liver injury and inflammation, which were further exacerbated by alcohol feeding. Seahorse flux and unbiased metabolomics analysis showed alcohol intake increased mitochondria oxygen consumption and hepatic nicotinamide adenine dinucleotide (NAD + ), acylcarnitine, and ketone levels, which were attenuated in L‐DRP1 KO mice, suggesting that loss of hepatic DRP1 leads to maladaptation to alcohol‐induced metabolic stress. RNA‐sequencing and real‐time quantitative PCR analysis revealed increased gene expression of the cGAS–stimulator of interferon genes (STING)–interferon pathway in L‐DRP1 KO mice regardless of alcohol feeding. Alcohol‐fed L‐DRP1 KO mice had increased cytosolic mtDNA and mitochondrial dysfunction leading to increased activation of cGAS‐STING‐interferon signaling pathways and liver injury. Conclusion: Alcohol consumption decreases hepatic DRP1 resulting in increased megamitochondria and mitochondrial maladaptation that promotes AH by mitochondria‐mediated inflammation and cell injury.
Obesity in Relation to Renal Cell Carcinoma Incidence and Survival in Three Prospective Studies
Authors: Rebecca E. Graff, Kathryn M. Wilson, Alejandro Sanchez, Steven L. Chang, David F. McDermott, Toni K. Choueiri, Eunyoung Cho, Sabina Signoretti, Edward L. Giovannucci, Mark A. Preston
Journal: European Urology (2022)
Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses
Authors: Mohamad-Gabriel Alameh, István Tombácz, Emily Bettini, Katlyn Lederer, Chutamath Sittplangkoon, Joel R. Wilmore, Brian T. Gaudette, Ousamah Y. Soliman, Matthew Pine, Philip Hicks, Tomaz B. Manzoni, James J. Knox, John L. Johnson, Dorottya Laczkó, Hiromi Muramatsu, Benjamin Davis, Wenzhao Meng, Aaron M. Rosenfeld, Shirin Strohmeier, Paulo J.C. Lin, Barbara L. Mui, Ying K. Tam, Katalin Karikó, Alain Jacquet, Florian Krammer, Paul Bates, Michael P. Cancro, Drew Weissman, Eline T. Luning Prak, David Allman, Michela Locci, Norbert Pardi
Journal: Immunity (2022)
High‐dimensional immune profiles correlate with phenotypes of peanut allergy during food‐allergic reactions
Authors: Julia Klueber, Rebecca Czolk, Françoise Codreanu‐Morel, Guillem Montamat, Dominique Revets, Maria Konstantinou, Antonio Cosma, Oliver Hunewald, Per Stahl Skov, Wim Ammerlaan, Christiane Hilger, Carsten Bindslev‐Jensen, Markus Ollert, Annette Kuehn
Journal: Allergy (2022)

Food challenges carry a burden of safety, effort and resources. Clinical reactivity and presentation, such as thresholds and symptoms, are considered challenging to predict ex vivo.To identify changes of peripheral immune signatures during oral food challenges (OFC) that correlate with the clinical outcome in patients with peanut allergy (PA).Children with a positive (OFC+ , n = 16) or a negative (OFC- , n = 10) OFC-outcome were included (controls, n = 7). Single-cell mass cytometry/unsupervised analysis allowed unbiased immunophenotyping during OFC.Peripheral immune profiles correlated with OFC outcome. OFC+ -profiles revealed mainly decreased Th2 cells, memory Treg and activated NK cells, which had an increased homing marker expression signifying immune cell migration into effector tissues along with symptom onset. OFC- -profiles had also signs of ongoing inflammation, but with a signature of a controlled response, lacking homing marker expression and featuring a concomitant increase of Th2-shifted CD4+ T cells and Treg cells. Low versus high threshold reactivity-groups had differential frequencies of intermediate monocytes and myeloid dendritic cells at baseline. Low threshold was associated with increased CD8+ T cells and reduced memory cells (central memory [CM] CD4+ [Th2] T cells, CM CD8+ T cells, Treg). Immune signatures also discriminated patients with preferential skin versus gastrointestinal symptoms, whereby skin signs correlated with increased expression of CCR4, a molecule enabling skin trafficking, on various immune cell types.We showed that peripheral immune signatures reflected dynamics of clinical outcome during OFC with peanut. Those immune alterations hold promise as a basis for predictive OFC biomarker discovery to monitor disease outcome and therapy of PA.
Trends in Acute Hepatitis of Unspecified Etiology and Adenovirus Stool Testing Results in Children — United States, 2017–2022
Authors: Anita K. Kambhampati, Rachel M. Burke, Stephanie Dietz, Michael Sheppard, Olivia Almendares, Julia M. Baker, Jordan Cates, Zachary Stein, Dylan Johns, Amanda R. Smith, Lara Bull-Otterson, Megan G. Hofmeister, Stacy Cobb, Suzanne E. Dale, Karl A. Soetebier, Caelin C. Potts, Jennifer Adjemian, Aaron Kite-Powell, Kathleen P. Hartnett, Hannah L. Kirking, David Sugerman, Umesh D. Parashar, Jacqueline E. Tate
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

In November 2021, CDC was notified of a cluster of previously healthy children with hepatitis of unknown etiology evaluated at a single U.S. hospital (1). On April 21, 2022, following an investigation of this cluster and reports of similar cases in Europe (2,3), a health advisory* was issued requesting U.S. providers to report pediatric cases† of hepatitis of unknown etiology to public health authorities. In the United States and Europe, many of these patients have also received positive adenovirus test results (1,3). Typed specimens have indicated adenovirus type 41, which typically causes gastroenteritis (1,3). Although adenovirus hepatitis has been reported in immunocompromised persons, adenovirus is not a recognized cause of hepatitis in healthy children (4). Because neither acute hepatitis of unknown etiology nor adenovirus type 41 is reportable in the United States, it is unclear whether either has recently increased above historical levels. Data from four sources were analyzed to assess trends in hepatitis-associated emergency department (ED) visits and hospitalizations, liver transplants, and adenovirus stool testing results among children in the United States. Because of potential changes in health care-seeking behavior during 2020-2021, data from October 2021-March 2022 were compared with a pre-COVID-19 pandemic baseline. These data do not suggest an increase in pediatric hepatitis or adenovirus types 40/41 above baseline levels. Pediatric hepatitis is rare, and the relatively low weekly and monthly counts of associated outcomes limit the ability to interpret small changes in incidence. Ongoing assessment of trends, in addition to enhanced epidemiologic investigations, will help contextualize reported cases of acute hepatitis of unknown etiology in U.S. children.
Addressing the environmental sustainability of eye health-care delivery: a scoping review
Authors: John C Buchan, Cassandra L Thiel, Annalien Steyn, John Somner, Rengaraj Venkatesh, Matthew J Burton, Jacqueline Ramke
Journal: The Lancet Planetary Health (2022)

The demand for eye care-the most common medical speciality in some countries-is increasing globally due to both demographic change and the development of eye health-care services in low-income and middle-income countries. This expansion of service provision needs to be environmentally sustainable. We conducted a scoping review to establish the nature and extent of the literature describing the environmental costs of delivering eye-care services, identify interventions to diminish the environmental impact of eye care, and identify key sustainability themes that are not yet being addressed. We identified 16 peer-reviewed articles for analysis, all published since 2009. Despite a paucity of research evidence, there is a need for the measurement of environmental impacts associated with eye care to be standardised along with the methodological tools to assess these impacts. The vastly different environmental costs of delivering clinical services with similar clinical outcomes in different regulatory settings is striking; in one example, a phacoemulsification cataract extraction in a UK hospital produced more than 20 times the greenhouse gas emission of the same procedure in an Indian hospital. The environmental costs must be systematically included when evaluating the risks and benefits of new interventions or policies aimed at promoting safety in high-income countries.